PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 28533928-8 2017 CONCLUSION: Leu amplifies the effects of NA on lipid metabolism, hyperlipidemia and atherosclerosis in mice, at least in part by activation of the AMPK/Sirt1 axis. Leucine 12-15 sirtuin 1 Mus musculus 152-157 28533928-0 2017 Leucine-nicotinic acid synergy stimulates AMPK/Sirt1 signaling and regulates lipid metabolism and lifespan in Caenorhabditis elegans, and hyperlipidemia and atherosclerosis in mice. Leucine 0-7 sirtuin 1 Mus musculus 47-52 28533928-2 2017 Leucine (Leu) stimulates the AMPK/Sirt1 axis and amplifies the effects of other AMPK/Sirt1 activating compounds. Leucine 0-7 sirtuin 1 Mus musculus 34-39 28533928-2 2017 Leucine (Leu) stimulates the AMPK/Sirt1 axis and amplifies the effects of other AMPK/Sirt1 activating compounds. Leucine 0-7 sirtuin 1 Mus musculus 85-90 28533928-2 2017 Leucine (Leu) stimulates the AMPK/Sirt1 axis and amplifies the effects of other AMPK/Sirt1 activating compounds. Leucine 0-3 sirtuin 1 Mus musculus 34-39 28533928-2 2017 Leucine (Leu) stimulates the AMPK/Sirt1 axis and amplifies the effects of other AMPK/Sirt1 activating compounds. Leucine 0-3 sirtuin 1 Mus musculus 85-90 32758058-8 2020 Low-dose (10 nM) NAD+ precursors (nicotinic acid, nicotinamide mononucleotide, and nicotinamide riboside) synergized with leucine to increase Sirt1 activity in adipocytes, hepatocytes, and muscle cells (30-100%, P < .01) and lifespan in Caenorhabditis elegans (25%, P = .025) and to significantly regress atherosclerotic lesion size and macrophage infiltration in a mouse model of atherosclerosis. Leucine 122-129 sirtuin 1 Mus musculus 142-147 32758058-9 2020 Thus, synergistic activation of Sirt1 using leucine and a co-activator exerts pleiotropic effects impacting cardiometabolic endpoints. Leucine 44-51 sirtuin 1 Mus musculus 32-37 30523660-7 2019 We also found that AMPKalpha1 siRNA, AMPK inhibitor compound C, or Sirt1 inhibitor EX527 attenuated the positive effect of leucine on slow-twitch muscle fibers and mitochondrial function-related gene expression. Leucine 123-130 sirtuin 1 Mus musculus 67-72 30523660-8 2019 Finally, we showed that Sirt1 was required for leucine-induced AMPK activation. Leucine 47-54 sirtuin 1 Mus musculus 24-29 30523660-9 2019 Our results provide, for the first time, evidence that leucine induces slow-twitch muscle fibers expression and improves mitochondrial function through Sirt1/AMPK signaling pathway in porcine skeletal muscle satellite cells. Leucine 55-62 sirtuin 1 Mus musculus 152-157 22913271-9 2012 CONCLUSION: These data demonstrate that either leucine or its metabolite HMB may be combined with a low concentration of resveratrol to exert synergistic effects on Sirt1-dependent outcomes; this may result in more practical dosing of resveratrol in the management of obesity, insulin-resistance and diabetes. Leucine 47-54 sirtuin 1 Mus musculus 165-170 25858853-2 2015 Leucine (Leu) activates Sirt1 by lowering its Km for NAD(+) and potentiates other sirtuin/AMPK-activators, resulting in improvement of insulin sensitivity. Leucine 0-7 sirtuin 1 Mus musculus 24-29 25858853-2 2015 Leucine (Leu) activates Sirt1 by lowering its Km for NAD(+) and potentiates other sirtuin/AMPK-activators, resulting in improvement of insulin sensitivity. Leucine 0-3 sirtuin 1 Mus musculus 24-29 25858853-5 2015 The effects of Leu on Met stimulation of Sirt1 and AMPK activities were further evaluated in adipocytes. Leucine 15-18 sirtuin 1 Mus musculus 41-46 25858853-6 2015 RESULTS: Sub-therapeutic levels of Met combined with Leu resulted in increases in Sirt1 activity and in tissue P-AMPK/AMPK ratio and corresponding dose-responsive improvements in fasting and post-prandial glucose, in glucose response to an insulin tolerance test and in the area under the curve in glucose tolerance tests. Leucine 53-56 sirtuin 1 Mus musculus 82-87 22967499-0 2012 Leucine supplementation increases SIRT1 expression and prevents mitochondrial dysfunction and metabolic disorders in high-fat diet-induced obese mice. Leucine 0-7 sirtuin 1 Mus musculus 34-39 22967499-7 2012 Addition of leucine to HFD correlated with increased expression of SIRT1 and NAMPT (nicotinamide phosphoribosyltransferase) as well as higher intracellular NAD(+) levels, which decreased acetylation of peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC1alpha) and forkhead box O1 (FoxO1). Leucine 12-19 sirtuin 1 Mus musculus 67-72 22967499-11 2012 These data suggest that increased expression of SIRT1 after leucine supplementation may lead to reduced acetylation of PGC1alpha and FoxO1, which is associated with attenuation of HFD-induced mitochondrial dysfunction, insulin resistance, and obesity. Leucine 60-67 sirtuin 1 Mus musculus 48-53 27456392-1 2016 BACKGROUND: We have previously shown leucine (Leu) to activate Sirt1 by lowering its KM for NAD+, thereby amplifying the effects of other sirtuin activators and improving insulin sensitivity. Leucine 37-44 sirtuin 1 Mus musculus 63-68 27456392-1 2016 BACKGROUND: We have previously shown leucine (Leu) to activate Sirt1 by lowering its KM for NAD+, thereby amplifying the effects of other sirtuin activators and improving insulin sensitivity. Leucine 46-49 sirtuin 1 Mus musculus 63-68 27456392-2 2016 Metformin (Met) converges on this pathway both indirectly (via AMPK) and by direct activation of Sirt1, and we recently found Leu to synergize with Met to improve insulin sensitivity and glycemic control while achieving ~80% dose-reduction in diet-induced obese mice. Leucine 126-129 sirtuin 1 Mus musculus 97-102 27456392-6 2016 RESULTS: Leu (0.5mmol/L)+Met (50-100mumol/L) synergistically activated Sirt1 (p<0.001) at low (<=100mumol/L) NAD+ levels while Met exerted no independent effect. Leucine 9-12 sirtuin 1 Mus musculus 71-76 27456392-12 2016 CONCLUSION: Thus, Leu and Met synergize to enable Sirt1 activation at low NAD+ concentrations (typical of energy replete states). Leucine 18-21 sirtuin 1 Mus musculus 50-55 28042486-2 2016 L-leucine, an allosteric Sirt1 activator, synergizes with low doses of metformin or sildenafil on the AMPK-eNOS-Sirt1 pathway to reverse mild NAFLD in preclinical mouse models. Leucine 0-9 sirtuin 1 Mus musculus 25-30 28042486-2 2016 L-leucine, an allosteric Sirt1 activator, synergizes with low doses of metformin or sildenafil on the AMPK-eNOS-Sirt1 pathway to reverse mild NAFLD in preclinical mouse models. Leucine 0-9 sirtuin 1 Mus musculus 112-117 22913271-2 2012 We have shown leucine to increase mitochondrial biogenesis and fat oxidation via Sirt1 dependent pathways. Leucine 14-21 sirtuin 1 Mus musculus 81-86 22913271-8 2012 Similarly, 6-week feeding of low-dose resveratrol combined with either leucine or its metabolite HMB to DIO mice increased adipose Sirt1 activity, muscle glucose and palmitate uptake (measured via PET/CT), insulin sensitivity (HOMAIR), improved inflammatory stress biomarkers (CRP, IL-6, MCP-1, adiponectin) and reduced adiposity comparable to the effects of high dose resveratrol, while low-dose resveratrol exerted no independent effect. Leucine 71-78 sirtuin 1 Mus musculus 131-136 20851890-3 2010 Here, we show that RSV inhibits insulin- and leucine-stimulated mTOR signaling in C2C12 fibroblasts via a Sirt1-independent mechanism. Leucine 45-52 sirtuin 1 Mus musculus 106-111 19500359-8 2009 Leucine also stimulated mitochondrial biogenesis genes SIRT-1, PGC-1alpha and NRF-1 as well as mitochondrial component genes UCP3, COX, and NADH expression by 3-5 fold in C2C12 cells (p < 0.003). Leucine 0-7 sirtuin 1 Mus musculus 55-61 19500359-12 2009 Transfection of C2C12 myocytes with SIRT-1 siRNA resulted in parallel suppression of SIRT-1 expression and leucine-induced stimulation of PGC-1alpha and NRF-1, indicating that SIRT-1 mediates leucine induced mitochondrial biogenesis in muscle cells. Leucine 107-114 sirtuin 1 Mus musculus 36-42 19500359-12 2009 Transfection of C2C12 myocytes with SIRT-1 siRNA resulted in parallel suppression of SIRT-1 expression and leucine-induced stimulation of PGC-1alpha and NRF-1, indicating that SIRT-1 mediates leucine induced mitochondrial biogenesis in muscle cells. Leucine 192-199 sirtuin 1 Mus musculus 36-42 34881260-8 2021 High dose of leucine supplementation could promote skeletal muscle health in aging mice via regulating AMPKalpha/SIRT1/PGC-1alpha. Leucine 13-20 sirtuin 1 Mus musculus 113-118